West Nile virus (WNV) is transmitted by mosquitoes and can cause illness in humans ranging from mild fever to encephalitis. In 2002, a total of 4,156 WNV cases were reported in the United States; 329 were in Louisiana. To estimate the economic impact of the 2002 WNV epidemic in Louisiana, we collected data from hospitals, a patient questionnaire, and public offices. Hospital charges were converted to economic costs by using Medicare cost-to-charge ratios. The estimated cost of the Louisiana epidemic was US 20.1 million dollars from June 2002 to February 2003, including a US 10.9 million dollars cost of illness (US 4.4 million dollars medical and US 6.5 million dollars nonmedical costs) and a US 9.2 million dollars cost of public health response. These data indicate a substantial short-term cost of the WNV disease epidemic in Louisiana.